Evidence map›Paper›PMID 27042676›Full record

ArticleAnnals of clinical and translational neurology2016

CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios: better diagnostic markers of Alzheimer disease.

Shorena Janelidze, Henrik Zetterberg, Niklas Mattsson, Sebastian Palmqvist, Hugo Vanderstichele, Olof Lindberg, Danielle van Westen, Erik Stomrud, Lennart Minthon, Kaj Blennow and 2 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of clinical and translational neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01208675 (The Swedish BioFINDER Study), which is not on this map. Cited by 262 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
262citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01208675 completednot on this map

The Swedish BioFINDER Study: Early Diagnosis of Alzheimer's Disease - a Multidisciplinary Approach

TypeobservationalSponsorSkane University HospitalRan2010 to 2024Enrolled1,150ConditionsMild Cognitive Impairment, Alzheimer's Disease, Dementia With Lewy Bodies, Vascular Dementia
3 · Its place in the literature

Who cites it

262 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Association of CSF AβNeurology · 2022
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  14. Sex differences in Alzheimer's disease plasma biomarker levels and clinical utility.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  20. Review

202 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Shorena JanelidzeClinical Memory Research Unit Department of Clinical Sciences, Malmö Lund University Lund Sweden.
Henrik ZetterbergClinical Neurochemistry Laboratory Institute of Neuroscience and Physiology Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden; Department of Molecular Neuroscience UCL Institute of Neurology Queen Square London United Kingdom.
Niklas MattssonClinical Memory Research Unit Department of Clinical Sciences, Malmö Lund University Lund Sweden; Memory Clinic Skåne University Hospital Malmö Sweden.
Sebastian PalmqvistClinical Memory Research Unit Department of Clinical Sciences, Malmö Lund University Lund Sweden; Department of Neurology Skåne University Hospital Malmö Sweden.
Hugo VandersticheleADx Neuro Sciences Gent Belgium.
Olof LindbergClinical Memory Research Unit Department of Clinical Sciences, Malmö Lund University Lund Sweden.
Danielle van WestenDepartment of Clinical Sciences Diagnostic Radiology Lund University Lund Sweden; Imaging and Function Skåne University Health Care Lund Sweden.
Erik StomrudClinical Memory Research Unit Department of Clinical Sciences, Malmö Lund University Lund Sweden; Memory Clinic Skåne University Hospital Malmö Sweden.
Lennart MinthonClinical Memory Research Unit Department of Clinical Sciences, Malmö Lund University Lund Sweden; Memory Clinic Skåne University Hospital Malmö Sweden.
Kaj BlennowClinical Neurochemistry Laboratory Institute of Neuroscience and Physiology Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden.
Swedish BioFINDER study group
Oskar HanssonClinical Memory Research Unit Department of Clinical Sciences, Malmö Lund University Lund Sweden; Memory Clinic Skåne University Hospital Malmö Sweden.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThe diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) must be improved before widespread clinical use. This study aimed to determine whether CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios are better diagnostic biomarkers of AD during both predementia and dementia stages in comparison to CSF Aβ42 alone.

methodsThe study comprised three different cohorts (n = 1182) in whom CSF levels of Aβ42, Aβ40, and Aβ38 were assessed. CSF Aβs were quantified using three different immunoassays (Euroimmun, Meso Scale Discovery, Quanterix). As reference standard, we used either amyloid ((18)F-flutemetamol) positron emission tomography (PET) imaging (n = 215) or clinical diagnosis (n = 967) of well-characterized patients.

resultsWhen using three different immunoassays in cases with subjective cognitive decline and mild cognitive impairment, the CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios were significantly better predictors of abnormal amyloid PET than CSF Aβ42. Lower Aβ42, Aβ42/Aβ40, and Aβ42/Aβ38 ratios, but not Aβ40 and Aβ38, correlated with smaller hippocampal volumes measured by magnetic resonance imaging. However, lower Aβ38, Aβ40, and Aβ42, but not the ratios, correlated with non-AD-specific subcortical changes, that is, larger lateral ventricles and white matter lesions. Further, the Aβ42/Aβ40 and Aβ42/Aβ38 ratios showed increased accuracy compared to Aβ42 when distinguishing AD from dementia with Lewy bodies or Parkinson's disease dementia and subcortical vascular dementia, where all Aβs (including Aβ42) were decreased.

interpretationThe CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios are significantly better than CSF Aβ42 to detect brain amyloid deposition in prodromal AD and to differentiate AD dementia from non-AD dementias. The ratios reflect AD-type pathology better, whereas decline in CSF Aβ42 is also associated with non-AD subcortical pathologies. These findings strongly suggest that the ratios rather than CSF Aβ42 should be used in the clinical work-up of AD.

Identifiers

PMID27042676
PMCPMC4774260

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.